rs148344039

Variant names:

• chr16-15694172-C-A
• NM_017668.3:c.711C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-15694172-C-A
• chr16-15694172-C-G
• chr16-15694172-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017668.3(NDE1):​c.711C>A​(p.Asp237Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDE1 NM_017668.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038899153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_017668.3	c.711C>A	p.Asp237Glu	missense_variant	Exon 7 of 9	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6	c.711C>A	p.Asp237Glu	missense_variant	Exon 7 of 9	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460358 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.031
DANN	Benign	0.47
DEOGEN2	Benign	0.046	T;T;T;T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.68	.;T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.039	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L;L;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.16	N;N;.;.;.
REVEL	Benign	0.039
Sift	Benign	0.45	T;T;.;.;.
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.0020	B;B;.;.;.
Vest4		0.14
MutPred		0.29		Gain of glycosylation at S239 (P = 0.1421);Gain of glycosylation at S239 (P = 0.1421);.;.;.;
MVP		0.35
MPC		0.059
ClinPred		0.068	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-15788029;